Jacob Korula

Endoscopic sclerotherapy as compared with endoscopic ligation for bleeding esophageal varices

Abstract Background. Endoscopic sclerotherapy is an accepted treatment for bleeding esophageal varices, but it is associated with substantial local and systemic complications. Endoscopic ligation, a new form of endoscopic treatment for bleeding varices, may be safer. We compared the effectiveness and safety of the two techniques. Methods. In this randomized trial we compared endoscopic sclerotherapy and endoscopic ligation in 129 patients with cirrhosis who had proved bleeding from esophageal varices. Sixty-five patients were treated with sclerotherapy, and 64 with ligation. Initial treatment for acute bleeding was followed by elective retreatment to eradicate varices. The patients were followed for a mean of 10 months, during which we determined the incidence of complications and recurrences of bleeding, the number of treatments needed to eradicate varices, and survival. Results. Active bleeding at the first treatment was controlled by sclerotherapy in 10 of 13 patients (77 percent) and by ligation in 12...

Demonstration of two distinct subsets of gastric varices. Observations during a seven-year study of endoscopic sclerotherapy.

Over a seven-year period, assessment of gastric varices was made on 225 patients receiving endoscopic sclerotherapy for variceal hemorrhage. Of 170 patients with complete data, gastric varices were observed in 26 (15.3%). Importantly, two distinct subsets of gastric varices were identified: varices distal to the gastroesophageal junction without extension into the fundus, termed “junctional varices”, occurred in 11.2%, and varices that were confined only to the fundus, termed “fundal varices”, occurred less frequently in 4.1%. Although rebleeding was increased in both subsets of gastric varices, junctional varices were more amenable to sclerotherapy. Patients with fundal varices (N=7) had a significantly higher rebleeding rate, increased complications with sclerotherapy, and significantly decreased survival (P<0.005) when compared to patients with esophageal varices alone (N=87) who were followed for more than three months. Cumulative survival was not significantly different (P<0.08) in patients with junctional varices (N=19) when compared with patients with esophageal varices alone. We conclude that not all patients with gastric varices have a poor result with sclerotherapy. Recognition of these subsets may improve treatment strategies in patients with gastric varices.

Diagnostic features of tuberculous peritonitis in the absence and presence of chronic liver disease: A case control study

PURPOSE To determine diagnostic features of tuberculous peritonitis (TBP) in the absence and presence of chronic liver disease. PATIENTS AND METHODS Thirty-four patients with TBP (13 without [Group I] and 21 with chronic liver disease [Group II] and 26 controls with cirrhosis and uninfected ascites (Group III) were studied. RESULTS The clinical features in Groups I and II were similar and all patients had elevated ascitic fluid total mononuclear cell count. In Groups I, II, and III, respectively, ascitic fluid protein was > 25 g/L in 100% (13/13), 70% (14/20), and 0% (0/26); serum-ascites albumin gradient (SAAG) was > 11 g/L in 0% (0/13), 52% (11/21), and 96% (25/26), (0% [0/13], 71% [15/21], and 96% [25/26] after correction for serum globulin); and ascitic fluid lactate dehydrogenase (LDH) level was > 90 U/L in 100% (12/12), 84% (16/19), and 0% (0/20), respectively. In Groups I and II combined, ascitic fluid acid-fast stain was negative in all but Mycobacterium tuberculosis culture was positive in 45% (10/22); peritoneal nodules occurred in 94% (31/33), granulomas in 93% (28/30), and positive peritoneal M tuberculosis culture in 63% (10/16). CONCLUSIONS In patients with suspected TBP, ascitic fluid protein of > 25 g/L, SAAG of < 11 g/L and LDH of > 90 U/L have high sensitivity for the disease. With coexistent chronic liver disease, a lower protein level and higher SAAG are usually not helpful but LDH > 90 U/L is a useful parameter for screening. Diagnosis is best confirmed by laparoscopy with peritoneal biopsy and M tuberculosis culture.

The effects of chronic endoscopic variceal sclerotherapy on portal pressure in cirrhotics

The effect of obliterating esophageal varices by endoscopic sclerotherapy on portal pressure was prospectively studied in 11 cirrhotic patients with variceal hemorrhage. Portal venous pressure gradient, determined as the difference between transhepatic portal and hepatic vein pressure, increased by a mean of 31.1% +/- 14.5% in 8 (73%) and decreased by a mean of 30.1% +/- 11.7% in 3 (27%) patients, with no statistically significant change overall (P = 0.1). These changes in portal venous pressure gradient occurred despite an improvement in the laboratory and clinical parameters of hepatic function. Deep abdominal sonography with color flow imaging at variceal obliteration showed patent paraumbilical veins in 6 (55%) patients, 3 of whom had decreases in portal venous pressure gradient (29%, 19%, 42.5%) at variceal obliteration. In 5 (45%) patients without patent paraumbilical veins, a statistically significant increase in portal venous pressure gradient between initial endoscopic variceal sclerotherapy and variceal obliteration was noted (P = 0.008). Rebleeding (single episode in all 4 patients, before obliteration in 3 patients) occurred in those with an increase in portal venous pressure gradient; all patients with portal venous pressure gradient decreases were nonbleeders. No correlation between changes in portal venous pressure gradient and time to variceal obliteration, number of sclerotherapy treatments, or rebleeding episodes was observed. Thus, an increase in portal venous pressure gradient was noted in the majority of patients at variceal obliteration. Although the portal venous pressure gradient decrease may be explained by a patent paraumbilical vein, the mechanism of portal venous pressure gradient increase is not clear. It is speculated that this portal venous pressure gradient increase may be caused by an increase in collateral resistance or flow or a combination of both, resulting from obliteration of esophageal varices by endoscopic sclerotherapy.

Frequent endoscopic variceal sclerotherapy increases risk of complications - Prospective randomized controlled study of two treatment schedules

In an effort to determine the optimal dose and frequency of chronic endoscopic variceal sclerotherapy, a prospective randomized controlled study comparing two treatment schedules of sclerotherapy was carried out over a 21-month period. Patients with variceal hemorrhage were randomly assigned to receive sclerotherapy at weekly intervals using injection volumes of >15 cc at each treatment or at mean intervals of three days using volumes of <10 cc per treatment. Esophageal perforation occurred in three patients (15%) in the small-dose, frequent-injection group as compared to none in the large-dose weekly treatment group (P=0.07), leading to premature termination of the study. The mean time to rebleeding was significantly shorter in the small-dose, frequent-treatment group (P=0.05). Variceal obliteration was achieved in a mean of 66% of patients in both groups with no difference in the time to obliteration or the frequency of other complications. Sclerotherapy offered at less than weekly intervals is less effective and is associated with an increased frequency of serious and life threatening complications.

Failure of ketoconazole as anti-androgen therapy in nonresectable primary hepatocellular carcinoma

Lacking a treatment for nonresectable hepatocellular carcinoma (HCC), we have utilized the androgen antagonist properties of ketoconazole in treating eight patients, seven men and one woman, with HCC, which, in view of a higher prevalence of HCC in men, seems to be androgen dependent. Response to treatment was determined by grading symptoms, serum alphafetoprotein, alteration in tumor size, and duration of survival. No patient had any significant side-effects from ketoconazole. No symptomatic improvement occurred, percent tumor size increased from 38.6 +/- 12, mean +/- SEM, to 44.4 +/- 12, and mean survival in six patients who were followed until death was less than 8 weeks from diagnosis. Anti-androgenic therapy with ketoconazole was not effective in any of these patients.

Portal vein thrombosis following endoscopic variceal sclerotherapy. Prospective controlled comparison in patients with cirrhosis.

The association between portal vein thrombosis (PVT) and prior endoscopic variceal sclerotherapy has been suggested but remains unproven. The aim of this study was to compare the incidence of PVT in patients who had received sclerotherapy for esophageal variceal hemorrhage to a control group of cirrhotic patients with portal hypertension who had not received sclerotherapy. Doppler ultrasound was used to assess PVT in 48 patients (group 1) who had received sclerotherapy for variceal hemorrhage as well as in 52 patients (group 3) with cirrhosis and portal hypertension who had not received sclerotherapy. Assessment of PVT was made at the time of surgery in 24 patients (group 2) who had received sclerotherapy for variceal hemorrhage, failed therapy, and had portacaval shunt surgery or received liver transplantation for liver failure. One patient had splenectomy for symptoms related to a massively enlarged spleen. The incidence of PVT in group 1 was 10%, in group 2 was 13%, and in group 3 was 10%. The incidence of PVT in the three groups was not significantly different statistically. In this controlled study of patients with cirrhosis and portal hypertension, sclerotherapy does not increase the incidence of PVT.

Effects of sodium tetradecyl sulfate endoscopic variceal sclerotherapy on the esophagus. A prospective clinical and histopathologic study.

A prospective clinical, endoscopic, and histopathologic study of the esophagus was carried out in 24 patients with advanced liver disease who underwent esophageal variceal sclerotherapy (EVS) and who eventually came to autopsy. Patients were arbitrarily divided into three groups: acute (group I), intermediate (group II), and chronic (group III) based on the interval between the first EVS and death. EVS with sodium tetradecyl sulphate (STS) initially produced thrombosis with varying degrees of necrosis and inflammation followed by ulceration, recanalization, and eventually fibrosis with obliteration of varices. Recurrent variceal hemorrhage (VH) leading to death was highest in the acute group since all patients died of uncontrollable VH (100%); it ranged between 50-60% in both the intermediate and chronic groups. Despite variceal obliteration, recurrent hemorrhage developed in the chronic group due to gastric varices or other venous channels in the esophagus or stomach. Additionally, we describe findings not previously reported, such as the presence of sclerosant outside the varices after intravariceal injection, thrombosis of gastric varices after esophageal injections, and the development of muscular wall thickening.

Perforation of esophagus after endoscopic variceal sclerotherapy

To determine the true incidence of endoscopic variceal sclerotherapy (EVS) -related esophageal perforation, a retrospective analysis of 900 EVS procedures using sodium tetradecyl sulfate performed on 170 patients during a five-year period (1980–1985) was carried out. Autopsy data of all patients who received EVS and who died (32 patients, 100%) during this period were available to confirm the diagnosis of perforation. Esophageal perforation was confirmed in 5 (2.9%) and was seen in patients with advanced alcoholic liver disease. Importantly, most patients did not manifest features of an esophageal leak, but presented instead as a deterioration in condition and died after a mean (±sd) 14±5.2 days. Analysis of the clinical and EVS data reveals that the risk of developing perforation is high when EVS is performed during active bleeding. The extravariceal location of sclerosant and microabscesses may be important predisposing factors. In our experience largedose injection, deep ulceration, and balloon tamponade are less likely predisposing factors of this complication.

Analysis of Long-Term Endoscopic Surveillance During Follow-up After Variceal Sclerotherapy From a 13-Year Experience

PURPOSE To evaluate the course of patients with bleeding esophageal varices treated with endoscopic sclerotherapy after obliterating varices and to determine the cost benefits of long-term endoscopic surveillance from a retrospective analysis of a 13-year experience. LOCATION University-affiliated teaching hospital and county facility. METHODS Patients whose varices were obliterated by endoscopic sclerotherapy were considered for the study if they had a minimum of 12 months of follow-up. Sclerotherapy was initially performed weekly, increasing intervals to eventual yearly treatments. Varices were reobliterated if they reformed. Variables assessed were rebleeding, mortality, employment status, and cost based on allowable and reimbursed Medicare rates. RESULTS Of 324 patients who achieved variceal obliteration, analysis included 104 eligible patients who were followed up for > 12 months (41 +/- 28). Varices reformed in 73 patients (71%), mostly in the first year after obliteration or reobliteration. Abstinent alcoholic patients were least likely to reform varices. Nineteen patients (18%) had 23 rebleeding episodes, and in 10 patients (10%) portalsystemic shunt was placed. Survival was 84% and bleeding-related mortality was 6%. Significantly more patients were employed while on the program compared with entry. The yearly cost of treating variceal reformers (